Although domestic cigarette smoking is decreasing, there has been a threefold increase in small cigar smoking, and further increases are expected because cigars are not subject to the restrictions of the Family Smoking Prevention & Tobacco Control Act. The societal and personal health consequences of any tobacco consumption are intimately related to the characteristics of the product and how the product is used. Despite evidence suggesting that cigar smoke delivers nicotine (the addictive component) and more than 60 carcinogens, there are no systematic studies that consider both toxin delivery and the smoking behavior of various cigar products. The present proposal answers this deficiency by comparing cigarettes to three prototypical cigar products (PCP) (i.e., cigarillo, small cigar and conventional cigar) by examining behavioral aspects of smoking in a clinical study and the chemistry and particle distribution of mainstream smoke. In the clinical study, participants who smoke both cigarettes and cigars will be assigned to one of three experimental groups (cigarillo, small cigar, conventional cigar), based on their usual cigar product-25 participants/group. Puff topography and inhalation measures will be collected simultaneously while they smoke the cigar (at one visit) and their own brand cigarette (other visit). The prevailing view that cigar smoke is puffed only-not inhaled-may not be true for cigarillos and small cigars and may depend on the participant's smoking history. Chemical measures of acute (nicotine and CO boost) and chronic exposure (cotinine and 3-OH-cotinine NNAL, 1-HOP) will be obtained from the participants. The puffing profiles from the cigar and cigarette smoking will be recorded and used to drive the machine smoking of the PCPs and cigarettes in the chemical laboratory study. The mainstream smoke generated by machine smoking will be characterized by particle size (fine and ultrafine), distribution and gas-phase toxic/carcinogenic components. Identical analyses will be used on mainstream smoke from PCPs and five selected cigarettes (full flavor, light, ultra light, unfiltered and menthol) will be generated using two machine smoking protocols: one designed especially for cigars, and the other historically used for cigarettes. We will compare the delivery of nicotine and various carcinogens between cigarettes and PCPs, compare delivery between the three PCPs and compare nicotine and toxin exposure, puffing, and inhalation between the PCPs and cigarettes. PUBLIC HEALTH RELEVANCE: Data from these innovative studies that combine human smoking of PCPs and chemical analysis of their mainstream smoke provide information on toxin delivery, deposition of particles and the relation to locus of pathology informing the discussion of addictive and health risks of cigar smoking and regulatory decisions of cigar products. PUBLIC HEALTH RELEVANCE: Domestic cigar use is increasing and further increases are expected as a result of new regulations on cigarettes but not cigars; however, little is known about the patterns of use and the toxin delivery from newer cigar products that appear and are consumed like cigarettes. The proposed study will compare toxin delivery from cigarettes and three prototypical cigar products (i.e., cigarillo, small cigar, conventional cigar) in a clinical study that will assess inhalation and puffing patterns, and biomarkers of immediate and long term exposure, and laboratory studies that will determine particle size [distribution] and selected toxins/carcinogens in the mainstream smoke of the cigar products and cigarettes. These studies will be the first comprehensive examination of cigar smoking that integrates inhalation and puffing with mainstream smoke chemistry and the delivery of smoke constituents responsible for addiction and pathology.